Synthetic microfluidic systems for tumor metastasis
Inventors
Prabhakarpandian, Balabhaskar • Pant, Kapil
Assignees
Publication Number
US-9933413-B2
Publication Date
2018-04-03
Expiration Date
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
A method of assaying metastasis can include: providing a device of one of the embodiments; introducing the at least one cancer cell into the at least one internal chamber or at least one fluid channel; and studying metastasis of the at least one cancer cell. Optionally: introducing cancer cells into a first internal chamber; detecting escape of the cancer cell from the first internal chamber into the fluid channel; detecting migration of the cancer cell through the fluid channel; detecting adhesion of the cancer cell to a coating on the fluid channel; detecting invasion of the cancer cell into a second internal chamber from the fluid channel; or visualizing metastasis of the cancer cell with a visualization device.
Core Innovation
The invention includes a device and methodology to study and characterize tumor cell metastasis in physiologically realistic microenvironments, referred to as a MIcrofluidic MEtastatic Assay (MIME). The device is configured with an internal chamber and surrounding capillary channels to simulate the cancer metastasis multi-step process. The device and methodologies allow for the study and real-time visualization of cancer cells breaking the extracellular matrix in the tissue chamber, escaping into the circulatory system of the microfluidic pathway, adhering to vascular walls, and migrating/invading into other tissue chambers to proliferate.
The device provides an integrated microfluidic metastatic platform that can reproduce physiological features of a microenvironment, permit quantitative real-time visualization of the entire metastatic process, and be used as an in vitro model for developing therapeutics. The device can include an optically transparent disposable plastic body with a microcirculatory network and a simulated vascular wall with an endothelial layer growing thereon. The device is presented as a reproducible, screen-friendly approach that enables analysis of adhesion, circulation, migration, invasion, and targeted delivery in a flow- and morphology-realistic environment.
Claims Coverage
One independent claim identified. Six main inventive features extracted from the independent claim.
At least one first internal chamber configured for an internal cell culture
at least one first internal chamber configured for an internal cell culture
A first fluidic flow channel network fluidly coupled with the at least one first internal chamber
a first fluidic flow channel network fluidly coupled with the at least one first internal chamber, the first fluidic flow channel network comprising at least one first fluid flow channel bordering and surrounding the at least one first internal chamber that is configured for a channel cell culture, each first fluid flow channel having a single first fluid flow inlet and single first fluid flow outlet and being continuous between the single first fluid flow inlet and single first fluid flow outlet
At least one first wall having first gaps that fluidly couple the internal chamber with the first fluid flow channel
at least one first wall separating the at least one first internal chamber and the at least one first fluid flow channel, the at least one first wall having first gaps that fluidly couple the at least one first internal chamber with the at least one first fluid flow channel, wherein each first wall is continuous from the single first fluid flow inlet and single first fluid flow outlet
At least one second fluid flow channel surrounding the first fluid flow channel
at least one second fluid flow channel bordering and surrounding the at least one first fluid flow channel such that the at least one first fluid flow channel is between the at least one second fluid flow channel and at least one first internal chamber, each second fluid flow channel having a single second fluid flow inlet and single second fluid flow outlet and being continuous between the single second fluid flow inlet and single second fluid flow outlet
At least one second wall having second gaps that fluidly couple the first and second fluid flow channels
at least one second wall separating the at least one first fluid flow channel and at least one second fluid flow channel, the at least one second wall having second gaps that fluidly couple the at least one first flow fluid channel and at least one second fluid flow channel, wherein each second wall is continuous from the single second fluid flow inlet and single second fluid flow outlet
At least one cancer cell in the internal chamber or in the fluid flow channel network
at least one cancer cell in the at least one first internal chamber or in the fluid flow channel network fluidly coupled thereto
The independent claim defines a microfluidic cell culture device with nested, continuous fluid flow channel networks surrounding an internal chamber, porous separating walls with fluidic gaps, and inclusion of at least one cancer cell within the chamber or channel network.
Stated Advantages
Integrated tumor metastasis device
Flow- and morphologically realistic environment
Quantitative real-time visualization of adhesion, migration, invasion, and metastasis
Ability to screen new anti-tumor therapeutics and targeted drug delivery
Reduced reagent and cell use and disposable chips
Reproducible and screen-friendly approach to developing new therapies
Documented Applications
Assaying and characterizing tumor cell metastasis in vitro
Studying targeted therapy to tumor cells and inhibiting metastasis
Real-time visualization and quantitation of cell adhesion, migration, invasion, and circulation
Drug screening including nanoparticle- or nanopolymer-based delivery and siRNA/gene delivery
Studying endothelial adhesion and particle/cell adhesion under physiological flow
Investigations related to cancer research, angiogenesis, inflammation, wound healing, and radiation damage
BioMEMS development, hemodynamic and cellular analysis, microcirculation, tumor biology, targeted therapy, and oncology
Interested in licensing this patent?